Sandbox28

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Bejan Hakimi and Brendan Walker 3/4/09

GLYCOGEN SYNTHASE KINASE 3 BETA
Glycogen Synthase Kinase 3 Beta has beta sheet in the two opposite quadrants and alpha helices in the other two opposite quadrants. There are also two active sites that can be seen here: Active Sites

This view of the protein shows an ampiphilic character in regards to the protein containing a hydrophobic core (black) surrounded by hydrophilic surface residues (green) that stretch farther out from the protein than do the hydrophobic elements. This trend occurs throughout the protein for the most part and can be seen in both the alpha and beta structures and can be seen by rotating the protein. View 1.

Publication Abstract from PubMed

Glycogen synthase kinase 3 beta (GSK3 beta) plays a key role in insulin and Wnt signaling, phosphorylating downstream targets by default, and becoming inhibited following the extracellular signaling event. The crystal structure of human GSK3 beta shows a catalytically active conformation in the absence of activation-segment phosphorylation, with the sulphonate of a buffer molecule bridging the activation-segment and N-terminal domain in the same way as the phosphate group of the activation-segment phospho-Ser/Thr in other kinases. The location of this oxyanion binding site in the substrate binding cleft indicates direct coupling of P+4 phosphate-primed substrate binding and catalytic activation, explains the ability of GSK3 beta to processively hyperphosphorylate substrates with Ser/Thr pentad-repeats, and suggests a mechanism for autoinhibition in which the phosphorylated N terminus binds as a competitive pseudosubstrate with phospho-Ser 9 occupying the P+4 site.

Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition., Dajani R, Fraser E, Roe SM, Young N, Good V, Dale TC, Pearl LH, Cell. 2001 Jun 15;105(6):721-32. PMID:11440715

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.